Environmental pollution is a worldwide problem, heavy metals belonging to the most important pollutants. The progress of industries has lead to increased emission of pollutants into ecosystems. Manzala Lake is one of the most important aqua systems, which receives effluents discharges from heavily industrialized and highly populated settlements. Metals tend to accumulate in water and move up through the food chain. So, studies to ascertain the level of heavy metals in environment and determine potentially hazardous levels for human are necessary. In this study heavy metal (Pb, Cd, Fe, Cu, and Zn) were determined in different tissues (muscle, gill) of Tilapia nilotica from the south part of Manzala lake (Egypt) to assess the lake water pollution with those toxic metals. The range of Fe was (0.16-0.54 μg/L) in water from sampling sites, with no significant difference between the three sites, while, the level was (0.066-1.13 μg/g) in muscle and fish gills. The level of Zn was (0.08-0.26 μg/g) in muscle and fish gills, but longterm disposal of wastewater into the lake resulted in high level of Zn and Cu in the tissues and gills of the fish. The concentration of lead was (0.05-0.31 μg/L) in water with the highest level in site 3, the discharge point of industrial effluents and (0.09-0.46 ug/g) in muscle and fish gills. The levels of Pb in this study were higher than the maximum permissible limits (FAO, UNEP, FEPA, WHO and ECR. no 2360/ 2007) for human consumption. In conclusion, the levels of heavy metals observed in the fish and water samples can be considered as a serious matter. More safe and economic methods for the elimination of heavy metals from contaminated waters are needed and continuous assessment of the level of pollution of the lake waters and fish with heavy metals is also necessary. Safe disposals of domestic sewage and industrial effluents as well as enforcement of laws enacted to protect our environment are therefore advocated.